The treatment of many diseases and disorders of the eye, especially in case of degenerative or persistent conditions, poses challenges of achieving and maintaining adequate therapeutic drug concentrations within the eye and its surrounding structures. For instance, oral therapies for the eye often only result in negligible actual absorption of the drug in the ocular tissues due to low bioavailability of the drug. Ocular drug levels following systemic administration of drugs, are usually limited by the blood/ocular barriers (i.e. tight junctions between the endothelial cells of the capillaries), limiting entry of drugs into the eye. In addition, serious adverse side effects have been associated with systemic administration of certain drugs for use in treating eye-related disorders. For example, systemic treatments of the eye using the immune response modifier cyclosporine A, have the potential to cause nephrotoxicity or increase the risk of opportunistic infections.
The most common method of drug administration to the eyes is therefore by topical administration, which is mostly achieved by way of ophthalmic drops and/or topical ointments containing the medicament. This type of drug delivery however has only limited and often variable penetration to the anterior chamber of the eye. In addition, adequate therapeutic levels of the drug are rarely achieved and sustained in e.g. the middle or back portions of the eye. This is a major drawback, as the posterior chamber of the eye is a frequent site of inflammation or the site of action where ocular drug therapy should is targeted to for many indications. Topical administration in the form of drops and ointments also poses the difficulty of adjusting the dose, as patients often administer too much or too little of the composition. It is also the most difficult treatment option in which to achieve patient compliance, since patients tend to forget to apply the compositions, particularly in the treatment of degenerative or persistent conditions.
As an approach for circumventing the drawbacks encountered by local topical delivery, local therapy routes for the eye involving direct intravitreal injection of a drug through the sclera (i.e. the spherical, collagen-rich outer covering of the eye) have been tried.
However, the intravitreal injection delivery route tends to result in a short half life and rapid clearance of the drug, without sustained release capability being attained. Consequently, monthly injections are frequently required to maintain therapeutic ocular drug levels which is not practical for many patients, particularly in the treatment of degenerative or persistent conditions. Moreover, monthly intravitreal injections are not without risk, as some undesired effects associated with repeated injections can occur including sub-conjunctival hemorrhage, intraocular infections, worsening of pre-existing cataracts, accidental lesion to the lens, and/or retinal detachment.
Implantable intraocular sustained-release delivery devices have the potential to avoid the shortcomings and complications that can arise from both systemic and local therapies (i.e. topical administration or intravitreal injections). However, despite the variety of ocular implant devices which have been described and used in the art, the full potential of this therapy route has not been reached.
A common approach is the use of biodegradable implants (See U.S. Pat. Nos. 5,164,188, 5,824,072, 5,476,511, 4,997,652, 4,959,217, 4,668,506, and 4,144,317); however, such implants do not allow prolonged residence time with a guarantee of suitable release of the active substance (i.e. the release of the drug may change throughout the residence period). Other devices, such as the ones described in U.S. Pat. No. 4,014,335, 3,416,530 or 3,618,604, comprise multiple layers and are complicated in their design and manufacture, increasing the likelihood of product variability or the need to comprise additional osmotic or ionic agents which may not be compatible with the ocular environment.
Also, accidental movement of the insert in the eye is frequently observed, the insert passing either behind the eye or leaving the socket.
In view of the above, there remains a need in the art for improved sustained release intraocular drug delivery devices, which are simple to manufacture, and capable of releasing a therapeutic agent at a sustained and controlled rate for extended periods of time, while reducing the likelihood of implant rejection.
US 2006/0074487 describes a device configured for the sulcus of the eye. The device is used for treating an ocular condition linked to a diminution of the amplitude of the eye due to a loss of tension of the zonular fibres caused by an increase of the diameter of the lens. The device comprises a closed tubular envelope made of an elastic and fluid-impermeable material. The inner ring wall of the envelope delimits a lumen adapted to be filled with an incompressible fluid. The envelope can be impregnated by a composition containing an active ingredient or a combination of active ingredients of a medicine. This device does however not guarantee sustained and controlled release of the medicine(s).